The analysis of the effect of novel agent for bone metabolism on bone metastasis

• Project/Area Number: 23791668
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Jikei University School of Medicine
• Principal Investigator: MAEDA Kazuhiro 東京慈恵会医科大学, 医学部, 助教 (50548849)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Wntシグナル / 転移性骨腫瘍 / Ｗｎｔシグナル / 破骨細胞 / Wnt

Research Abstract

RANK is a receptor of RANKL which is an essential molecule for osteoclastogenesis. Previously, we reported that the Wnt5a-Ror2 pathway enhances the expression of RANK in macrophages. On the other hand, another group reported that the expression of RANK in tumor cells enhance bone metastasis. Taken together, these findings suggest that the Wnt expressed by tumor cells affects itself in an autocrine manner, and promotes bone metastasis through the induction of RANK expression.
To test this hypothesis, we performed experiments using cell lines which have affinity for the bone such as breast and prostate cancer cell lines. In results these cells highly expressed RANK, Wnt5a and Ror1/2 in comparison with control cells. These results indicate that Wnt5a expressed by tumor cells act on Ror2 expressed in itself in an autocrine manner, and enhanced bone metastasis through the induction of RANK expression in tumor cells.

Research Products

• [Journal Article] Wntシグナルとsclerostin (2014)
  • Author(s): 前田和洋,斎藤充,丸毛啓史
  • Journal Title: 腎と骨代謝 Volume: (in press)
• [Journal Article] Wnt signals and bone metabolism (2014)
  • Author(s): Maeda K, Saito M, Marumo K
  • Journal Title: J Phys Sports Med Volume: (in press)
  • NAID: 130004972983
  • Peer Reviewed
• [Journal Article] Noncanonical Wnt5a enhances Wnt/β-catenin signaling during osteoblastogenesis (2014)
  • Author(s): Okamoto M, Udagawa N, Uehara S, Maeda K, et al
  • Journal Title: Sci Rep Volume: 4 Pages: 4493-4493
  • Peer Reviewed
• [Journal Article] Noncanonical Wnt5a enhances Wnt/-catenin signaling during osteogenesis. (2014)
  • Author(s): Okamoto, M., Udagawa, N., Yamashita, T., Nakamichi, Y., Uehara, S., Kato, H., Saito, N., Minami, Y., Takahashi, N., Kobayashi, Y.
  • Journal Title: Sci. report Volume: 4 Issue: 1 Pages: 4493-4493
  • DOI: 10.1038/srep04493
  • Peer Reviewed / Open Access
• [Journal Article] 最新用語解説臨床Wnt非古典経路と骨疾患 (2013)
  • Author(s): 前田和洋,小林泰浩,高橋直之,丸毛啓史
  • Journal Title: 骨粗鬆症治療 Volume: 12 Pages: 130-134
  • URL: http://mol.medicalonline.jp/library/journal/download?GoodsID=ae6kotue/2013/001202/013&name=0130-0134j&UserID=202.223.144.130&base=jamas_pdf
• [Journal Article] 【Wnt協奏曲 : 新たな活性化機構と他の増殖・分化シグナルとの協調による形態形成】(第2部) Wntシグナルと幹細胞からの組織形態形成Wnt5a-Ror2シグナルによる破骨細胞分化制御 (2013)
  • Author(s): 小林泰浩,前田和洋,高橋直之
  • Journal Title: 細胞工学 Volume: 32 Pages: 414-418
  • URL: http://gakken-mesh.jp/journal/detail/9784780901412.html
• [Journal Article] Roles of Wnt signals in bone resorption during physiological and pathological states. (2013)
  • Author(s): Maeda K et al.
  • Journal Title: J Mol Med (Berl) Volume: 91 Issue: 1 Pages: 15-23
  • DOI: 10.1007/s00109-012-0974-0
  • Peer Reviewed / Open Access
• [Journal Article] 【Wnt協奏曲:新たな活性化機構と他の増殖・分化 シグナルとの協調による形態形成】 (第2部) Wntシグナルと幹細胞からの組織形態形成 Wnt5a-Ror2シグナルによる破骨細胞分化制御 (2013)
  • Author(s): 小林泰浩, 前田和洋, 高橋直之
  • Journal Title: 細胞工学 Volume: 32 Pages: 414-418
• [Journal Article] 最新用語解説 臨床 Wnt非古典経路と骨疾患 (2013)
  • Author(s): 前田和洋, 小林泰浩, 高橋直之, 丸毛啓史
  • Journal Title: 骨粗鬆症治療 Volume: 12 Pages: 130-134
• [Journal Article] Wnt5a-Ror2シグナルは破骨細胞形成を亢進する (2012)
  • Author(s): 小林泰浩,前田和洋,高橋直之
  • Journal Title: 実験医学 Volume: 30 Pages: 1933-1936
  • URL: http://www.fujisan.co.jp/product/1281679805/b/819655/
• [Journal Article] Wntによる破骨細胞の分化制御機構 (2012)
  • Author(s): 小林泰浩,前田和洋,上原俊介
  • Journal Title: 細胞 Volume: 44 Pages: 274-277
  • URL: http://hokuryukan-ns.co.jp/magazines/archives/2012/05/6_1.html
• [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda, K., Kobayashi, Y., Udagawa, N., Uehara, S., Ishihara, A., Mizoguchi, T., Kikuchi, Y., Takada, I., Kato, S., Kani, S., Nishita, M., Marumo, K., Martin, T.J., Minami, Y., Takahashi, N.
  • Journal Title: Nat.Med. Volume: (印刷中) Issue: 3 Pages: 405-12
  • DOI: 10.1038/nm.2653
  • Peer Reviewed
• [Journal Article] Regulatory Mechanism of Osteoclastogenesis by Receptor Activator of Nuclear Factor kappa B Ligand (RANKL) and Wnt Signals (2011)
  • Author(s): Takahashi N, Maeda K, Ishihara A, Uehara S, Kobayashi Y
  • Journal Title: Front Biosci Volume: 16 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Regulatory mechanism of osteoclastogenesis by Wnt signaling (2011)
  • Author(s): Kobayashi Y, Maeda K, Uehara S, Yamashita T, Takahashi N
  • Journal Title: Inflammation and Regeneration Volume: 31 Pages: 413-419
  • NAID: 130004943807
  • Peer Reviewed
• [Presentation] 基礎疾患を伴わない非クロストリジウム性母指ガス壊疽の1例 (2014)
  • Author(s): 前田和洋, 千野博之, 宇高潤, 奥津裕也, 湯川充人, 三橋真, 斎藤充, 大谷卓也, 丸毛啓史
  • Organizer: 第28回東日本手外科研究会
  • Place of Presentation: 東京
• [Presentation] 骨芽細胞系細胞と破骨細胞前駆細胞間のWnt5a-Ror2シグナルは破骨細胞分化を促進する (2013)
  • Author(s): 前田和洋
  • Organizer: 平成25年度日本整形外科学会研究奨励賞第二次選考会
  • Place of Presentation: 千葉
  • Year and Date: 2013-10-16
• [Presentation] 骨代謝におけるWntシグナルの役割 (2013)
  • Author(s): 前田和洋
  • Organizer: 第68回日本体力医学会ランチョンセミナー
  • Place of Presentation: 東京
  • Year and Date: 2013-09-23
• [Presentation] Wnt5a-Ror2 signaling boosts bone destruction in arthritis (2013)
  • Author(s): Maeda K, Kobayashi Y, Takahashi N, Marumo K
  • Organizer: JCR international school 2013
  • Place of Presentation: Karuizawa
  • Year and Date: 2013-08-02
• [Presentation] 破骨細胞研究の新展開―歴史から臨床応用、現状の問題点まで― (2013)
  • Author(s): 前田和洋
  • Organizer: 東京慈恵会医科大学大学院特別講義IV
  • Place of Presentation: 東京
  • Year and Date: 2013-05-31
• [Presentation] Wnt5a-Ror2 signaling boosts bone destruction in arthritis. (2013)
  • Author(s): Maeda K, Kobayashi Y, Takahashi N, Marumo K
  • Organizer: JCR international school 2013
  • Place of Presentation: Karuizawa
• [Presentation] 骨代謝におけるWntシグナルの役割 (2013)
  • Author(s): 前田和洋
  • Organizer: 第68回日本体力医学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Wnt5a-Ror2 signaling boosts bone destruction in arthritis (2012)
  • Author(s): Maeda K
  • Organizer: The 6^<th> Bone&Cartilage Frontier
  • Place of Presentation: Tokyo
  • Year and Date: 2012-11-17
• [Presentation] Wnt5a-Ror2シグナルは関節炎に伴う骨破壊を増悪する (2012)
  • Author(s): 小林泰浩,前田和洋,上原俊介,高田伊知郎,加藤茂明,丸毛啓史,宇田川信之,高橋直之
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-07-19
• [Presentation] Wnt5a-Ror2シグナルは関節炎に伴う骨破壊を増悪する (2012)
  • Author(s): 小林泰浩、前田和洋、上原俊介、高田伊知郎、加藤茂明、丸毛啓史、宇田川信之、高橋直之
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] Wnt5a-Ror2経路は関節炎における骨破壊を促進する (2012)
  • Author(s): 前田和洋
  • Organizer: 第6回骨・軟骨フロンティア
  • Place of Presentation: 東京
  • Invited
• [Presentation] Wnt非古典経路はRANKの発現を亢進し破骨細胞分化を促進する (2011)
  • Author(s): 前田和洋,小林泰浩,岡本正則,高田伊知郎,加藤茂明,可児修一,西田満,南康博,宇田川信之,丸毛啓史,高橋直之
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋
  • Year and Date: 2011-10-20
• [Presentation] Wnt非古典経路はRANKの発現を亢進し破骨細胞分化を促進する (2011)
  • Author(s): １．前田和洋、小林泰浩、岡本正則、高田伊知郎、加藤茂明、可児修一、西田満、南康博、宇田川信之、丸毛啓史、高橋直之
  • Organizer: 第26回 日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋
• [Remarks]
  • URL: http://www.jikei.ac.jp/academic/course/57_seikei.html
• [Remarks] 東京慈恵会医科大学 整形外科
  • URL: http://www.jikei.ac.jp/academic/course/57_seikei.html
• [Remarks]
  • URL: http://www.mdu.ac.jp/about/top/004102.html